This research is aimed at identifying etiologic factors in the development of dental caries. It employs animal models to identify the types of human oral organisms which possess cariogenic potential and to test the effects of inhibitory agents and dietary alterations on caries and the caries-associated microflora. Emphasis is on the potential cariogenicity of dental plaque organisms other than Streptotoccus mutans, since the role of S. mutans in caries causation is already well documented. Approximately 50 strains of human plaque lactobacilli representing 8 species have been tested in hamsters receiving a high sucrose diet (NIDR 2000). Three strains caused severe caries and the remainder were much less active. About 30 of the human strains of lactobacilli have been tested in gnotobiotic rats receiving Diet 2000 and all but a single strain of Lactobacillus lactis induced some caries, primarily of the molar fissures. Thus, while most lactobacilli are cariogenic under favorable environmental conditions, i.e. in the gnotobiotic rat, they may be blocked from expressing this potential in conventional animals by inability to compete with the indigenous oral microflora and establish themselves on the dentition in numbers sufficient to cause disease. The future course of this research will include attempts to determine the biochemical determinants of virulence (cariogenicity) in the lactobacilli, studies of their interactions with other oral organisms and the screening of still other plaque organisms for potential cariogenicity.